U5: CHROMOSOMAL ABERRATIONS + DELETION Flashcards
Tiny changes in the chromosome
Mutations
Structural or numerical change in the chromosome seen even in simple staining techniques
Aberrations
Test for copy number repeats or loss
CGH
There are variations from the wild-type condition in either chromosome structure or chromosome number
Chromosomal aberrations
This mechanism is seen when genes are inherited only from the mother.
Genomic imprinting
Special form of duplication seen in Huntington’s Disease.
Expansion of trinucleotide repeats
Variation in Chromosome Structure
Deletion
Duplication
Inversion
Translocation
Three broad categories of chromosome mutations
Chromosome Rearrangements
Aneuploidy
Polyploidy
Overall chromosome number is unaffected, but large pieces of chromosomes move
Chromosome Rearrangements
Trisomy 21, Klinefelter’s Syndrome, Turner’s Syndrome
Aneuploidy
These mutations alter chromosome structure
Chromosome Rearrangements
One or more individual chromosome pair has its number altered (either add or subtract)
Aneuploidy
One or more complete chromosome sets are added
Polyploidy
3n, 4n
Polyploidy
T/F: Aneuploidies present as one or more of the chromosomes in the pair.
True
In what phase do aneuploidies occur?
Meiosis
This refers to a pair of homologous chromosomes that has failed to separate or segregate at anaphase so both chromosomes of the pair pass to the same daughter cell.
Nondisjunction
This refers to chromosomes which does not properly separate, leaving one or two sex cells with an extra chromosome or with one less chromosome.
Nondisjunction
This can occur after nondisjunction during the mitotic cell division.
Mosaicism
Chromosomal disorders caused by this results in one line of cells with a chromosomal aberration while other lines may stay unchanged.
Mosaicism
T/F: Egg with monosomic conditions do not proceed to further fertilization.
True
pag trisomy daw pwede pa
2n + 1 = 7
Aneuploidy (Trisomy)
3n = 9
Polyploidy (Autotriploid) / Triploidy
2n = 6
Chromosome rearrangement (duplication)
Where can triploidies be found?
Plants
Chromosomal mutation that results in the doubling of a segment of a chromosome
Duplication
may nadadagdag lang
2n = 6
Chromosome rearrangement (Duplication)
Forms of Duplication
Tandem
Reverse
Terminal Tandem
This duplication is observed with the repeats in Huntington’s Disease.
Tandem Duplication
This duplication is observed with inversed sequences.
Reverse Duplication
This duplication is observed in the tips.
Terminal Tandem Duplication
Unbalanced set of chromosomes, relative gene dosage is upset
Aneuploidy
Loss of a single chromosome copy
Monosomic
Extra copies of single chromosome
Polysomic
T/F: Most chromosome abnormalities are lethal, frequently in spontaneous abortions.
True
Exceptions of Lethal Chromosome Abnormalities
Trisomy 13, 18, 21, and Sex Chromosomes
T/F: An extra X or Y chromosome usually has a relatively severe effect.
False
mild effect
Mild effect of extra sex chromosome
1) X chromosome inactivation/Dosage Compensation
2) Not much (essential) on the Y
Part of a chromosome present twice
Duplication
ISCN stands for?
International System for Human Cytogenomic Nomenclature
Abbreviations: dup
Duplication
dup(17p12)
Charcot-Marie-Tooth type 1A
FORMATIVE: Symptoms of Charcot-Marie-Tooth Disease
- Hammertoes
- Muscle Weakness
- Foot Drop
- Paralysis
- Numbness or tingling
- Creeping sensation in the legs
Duplication that is one right after the other
Tandem duplication
Duplication that is repeated in another part of the chromosome (self explanatory daw)
Displaced Duplication
ABEFCD EFGH
Displaced duplication
ABCD EFEFGH
Tandem duplication
ABCD FEEFGH
Reverse duplication
T/F: Individuals can be homozygous or heterozygous for duplications, it can happen only on one or both sister chromatids.
True
Worst form of duplication
Homozygosity
consider dosage = more or lesser effect
The more or less there is will reflect on expression of phenotype
Dosage
Significant effects on an individual’s phenotype is due to?
Unbalanced Gene Dosage
dapat di ka double dosage haha
In what phase of Meiosis does duplication arise in heterozygotes?
Prophase I and Synapsis
T/F: The duplicated region in Meiosis must loop out for synapsis to occur.
True
pag di nag loop, matatanggal yung region = loss of chromosomal content
Position Effect of Eye Size in Drosophilia
Duplication
T/F: 99% of duplications are often bad, and 1% of duplications allow evolution to proceed forward.
True
The process in which fetal hemoglobin was allowed to evolve.
in utero reproduction
easter egg!!
pag sinira m yng protein coding gene…
patay Ka!
- ian, 2024
duplicated genes lang ang paglaruan moh
T/F: Fetal hemoglobin is a result of duplication.
True
T/F: Fetus will still survive even if it shares a blood supply with the mother (adult hemoglobin.)
False
all hemoglobin (oxygen) will go straight to the mother since it is adult hemoglobin
Duplication result of extra #12 chromosome or usually a mixture of cells (mosaicism)
Pallister Killian Syndrome
Symptoms of Pallister Killian Syndrome
- Severe intellectual disability
- Poor muscle tone
- “Coarse” facial features
- Prominent forehead
T/F: People with Pallister Killian have a shortened lifespan, but may live up to their 40s.
True
Duplication of a small piece of Chromosome 17 in each cell
Potocki-Lupski syndrome
17p11.2
Potocki-Lupski syndrome
About 40% of babies with Potocki-Lupski present with?
heart defects
Symptoms of Potocki-Lupski
- hypotonia (weak muscle tone)
- dysphagia (swallowing difficulties)
- does not grow and gain weight
Multiple duplications/microdeletions of a CGG segment in the 5’ untranslated region of the FMR1 gene on X chromosome.
Fragile X Syndrome
Xq27
Fragile X Syndrome
Syndrome with repeated trinucleotide segments and express penetrance
Fragile X Syndrome
6-40 repetitions
Weak Form
41-60 repetitions
Middle Form
61-200 repetitions
Strong Form
> 200 repetitions
Full mutation/penetrance
T/F: The deleted segment in deletions can be located anywhere in the chromosome.
True
T/F: Fragile X Syndrome affects more women than men.
False
mas severe kay man kasi isa lang X nya
Symptoms of Fragile X Syndrome
- inherited mental retardation
- prognathism (small and long face, large ears)
Loss of segment of a chromosome
Deletion
How does deletion start?
Chromosomal breakage
Causes of Chromosomal Breakage
- Heat
- Ionizing radiation
- Viruses
- Transposable elements
- Errors in recombination
Examples of ionizing / high energy radiation
UV, X-ray, cosmic rays
These cause oncogenic or cancer cells.
Viruses
These are also known as jumping genes.
Transposable Elements
T/F: Deletion that spans the centromere causes a more fatal effect due to the chromosome being acentric.
True
Deletion that occurs towards the end of a chromosome
Terminal deletion
T/F: Deletion in the telomeric region does not affect gene expression.
True
pag may nasama from subtelomeric = incompatible na of life
Deletion that occurs from or in the interior of a chromosome.
Intercalary / Interstitial Deletion
Relatively small amount of deletion (up to 5mb that could include a dozen genes)
Microdeletion
Deletion that is most common cause of disease
Microdeletion
other deletions are large enough = incompatible of life
Deletion that is usually found in children with physical abnormalities
Microdeletion
T/F: Large deletions can be detected in karyotype as a shortened chromosome.
True
Centromeric deletion
No segregation during cell division
T/F: Recessive alleles express more readily when there are deletions.
True
no counteracting mechanism if deleted ang dominant gene
Abbreviations: -
Chromosome Deletions
Abbreviations: Δ (delta)
Microdeletions
Abbreviations: del
Deletions of Chromosome Parts
Deletion of number of pairs that is not evenly divisible by three
Frameshift mutation
Deletion that is evenly divisible by three
In-frame deletion
Genetic disorders from Deletions
- Male infertility
- Duchenne Muscular Dystrophy
- Cystic Fibrosis
- DiGeorge Syndrome
Deletions in SMN-encoding gene, and the most common genetic cause of infant death
Spinal Muscular Atrophy
Syndromes associated with both microdeletions and genomic imprinting
- Angelman syndrome
- Prader-Willi syndrome
5p-
Cri-du-chat Syndrome
Also known as “cry of the cat”, severe mental retardation
Cri-du-chat Syndrome
11q-
Wilms tumor
Kidney tumors, genitals and urinary tract abnormalities
Wilms tumor
13q-
Retinoblastoma
Cancer of the eye, increased risk of other cancers
Retinoblastoma
15q-
Prader-Willi Syndrome
Weak slow growth in infants, Obesity or compulsive eating in children and adults
Prader-Willi Syndrome
ΔF508
Cystic Fibrosis
coding for Phenylalanine
T/F: Patients with cri-du-chat die on their first year of life or in early stages of life.
True
CLL stands for?
Chronic Lymphocytic Leukemia
-13q14
Chronic Lymphocytic Leukemia
Prader-Willi: What bands of Chromosome 15 are deleted in the long arm?
q11 and q13
Loss of OCA2 gene in Chromosome 15
Angelman syndrome
Have happy or excitable personalities, causes delayed development, intellectual disability and seizures (more on Maternal)
Angelman syndrome
2/3 deletion type
Duchenne Muscular Dystrophy
Change in sequence of codons and render the protein is abnormal
Frameshift mutation
T/F: Even if you do not delete protein coding genes, it might still have an effect since there is a possibility that it is a region that codes for transcription factors.
True
Expected to be alive at least 5 years after diagnosis
Wilms Tumor
This significantly influence the prognosis of disease
Type, Size, Location of Deletion
Also a product of the deletion of Retinoblastoma protein
Chronic Lymphocytic Leukemia (CLL)
Accumulation of B lymphocytes, increased abnormal antibodies
Chronic Lymphocytic Leukemia (CLL)
What makes B cells immortal?
Loss of apoptopic factors
This syndrome has no cure, and requires constant treatment.
Angelman syndrome
This is also related to Albinism.
OCA2 gene
This refers to when both alleles come from either maternal or paternal.
Uniparental disomy
More maternal syndrome
Angelman syndrome
More paternal syndrome
Prader-Willi Syndrome
